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Kelsey Parnian
Writing 116
Professor Gibbons
April 9, 2012
Smoking Cessation
Abstract
With ongoing developmental research on smoking cessation, scientists come to results
today that bringing an end to smoking is possible. Smoking tends to be caused by people with
depression or high levels of stress. Psychological treatments, counseling, drugs, and many more
options, in relation to smoking cessation still need to be researched. Everyone is different
psychologically and mentally, and not all treatments will be effective for smokers. Nicotine is a
leading chemical in the factors of smoking. Varenicline and bupropion are two smoking
cessation treatments, sometimes used in conjunction to assist a smoker who desires to quit
smoking. Researchers also realized that smokers with psychiatric disorders tended to have more
severe effects to the drugs given when they tried to attempt smoking cessation. Standardized
MedDRA Query was used to test the levels of depression during smoking cessation. Much
research is still needing to be done to determine whether smoking cessation is directly related to
smoking cessation or if it is caused by the treatments given.
Introduction
Smoking is one of the principal causes of deaths, accounting for approximately 443,000
deaths, or 1 of every 5 deaths, in the United States each year (8,10,14). Current smokers, with
enough motivation and initiative, will put an effort into putting an end to their smoking, which is
also known as smoking cessation. Smokers are likely to have major depressive disorders, which
may be a symptom from smoking withdrawal. (6,3,14). As smokers look for options to quit
smoking, researchers discovered that some treatments were actually harmful, especially to
smokers with psychiatric disorders or a previous history of depression. Some treatments such as
varenicline along with bupropion were used to assist towards smoking cessation treatments.
Varenicline is a smoking cessation drug that is well known to give people severe side effects
such as: uncommon behavior, depression, and suicidal thoughts. Bupropion is an anti-depressant

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used to suppress the psychological effects and depression behavior of smokers. The effects of
these smoking cessation treatments were effective, however some studies have proved to show
negative effects on smokers.
Nicotine
Through the use of tobacco, people have consumed large amounts of nicotine, one of the
most heavily used addictive drugs, which is the leading preventable causes of diseases, disability,
and death in the U.S. (15). Nicotine enters the bloodstream within 7 seconds of smoking tobacco
(7). This harmful chemical not just runs through a person’s body, but affects the chemical
balances of the brain dramatically. It also activates areas of the brain that are involved in
producing the feelings of pleasure and reward raising the levels of a neurotransmitter called
dopamine (16). Dopamine is a neurotransmitter that helps control the brain’s reward and pleasure
centers (17,21).
The affects of nicotine explains why people who are emotionally, physically, or mentally
stressed feel the effects of sensual relief when smoking. Once someone feels the pleasurable
effects of smoking, the levels of nicotine and dopamine encourage the brain to continue wanting
the feeling, and thus creating an addiction for smoking. Nicotine is the main chemical that makes
it difficult for someone trying to quit smoking, because once someone begins smoking cessation,
they are consistently fighting with their body and brain psychologically to not give into the
feelings or sensations brought by the tobacco. When nicotine addicts stop smoking they may
suffer from restlessness, hunger, depression, headaches, irritability, insomnia, and weight gain
(16,14). These symptoms during smoking cessation are known as withdrawal symptoms.

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Varenicline with Depressive Behaviors/ Psychiatric Disorders
Varenicline is a drug used along with anti-depressants and counseling to assist people
with smoking cessation. It works by blocking the pleasant effects of nicotine (from smoking) in
the brain (19). Varenicline is believed to work, in part, by reducing craving responses to smoking
cues and by reducing general levels of craving (12).
The act of smoking is psychologically dependent, where people feel relaxed and relieved
after a cigarette, usually caused by some of the effects of nicotine. Because of this, smokers tend
to have depression setbacks while trying to quit smoking. Smoking cessation alone does not
generally cause suicidal thoughts or behaviors, but what may cause or enhance these effects are
the drugs prescribed.
Varenicline not only significantly attenuates the craving and withdrawal symptoms that
occur during smoking abstinence, but also significantly reduce the rewarding effects of nicotine
and delay smoking relapse (20). Varenicline can reportedly cause neuropsychiatric adverse
effects, some resulting in hospitalizations and/or suicides (11).
Varenicline boxes are sold with warnings about serious side effects most importantly it is
cautioned for people who obtain mental illnesses or psychiatric disorders. Some of the
precautionary side effects for these smokers using varenicline are: increased risk of erratic
behavior, agitation, suicidal attempt, depression, psychosis suicidal ideation, and depressed
mood (13,14,20). Patients with mental illnesses and took varenicline, experienced dangerous side
effects as mentioned earlier by Xi and Mcclure. The high rates of effects caused by these drugs
remains a question as a reason to why some smokers continue to smoke after attempting smoking
cessation. It seems that varencline did not help with the suppressing smoking cravings. During
each of the 5 weeks of assessment, smoking cues elicited significantly greater cravings than

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neutral cues. However, scientists found no evidence that varencline significantly affected cue-
specific craving and varenicline have yielded mixed results (12). This information conducted by
Gass, clearly tells us that scientists still do not have clear results on the affects of varencline for
most patients.
Bupropion
Bupropion is an anti-depressant usually prescribed to patients along with a smoking
cessation drug to act as a nicotine receptor. Bupropion is usually used to treat major depressive
disorders (4). It works by increasing certain types of activity in the brain (5). Bupropion is a
weak reuptake inhibitor of norepinephrine and dopamine and may produce mild stimulant-like
effects (2). When a smoker decides to quit smoking, they pick a date and commit themselves to
quit; taking bupropion helps the brain to psychologically be convinced they will quit smoking.
The treatment acts as a reducer that fires rates of noradrenergic neurons in the locus ceruleus.
The firing rates of dopaminergic neurons are reduced by bupropion in the A9 and A10 areas of
the brain, but only at very high doses (1). Bupropion is usually used or campared to varencline
and it works by increasing certain types of activity in the brain (5) to help the psychological
effect of smoking reduce. The odds ratio for bupropion was smaller than varenicline and the
results were similar when depression and suicidal/self-injurious behavior were examined
separately (14). Although not proven to be fully effective, bupropion used alone was
significantly longer compared to placebo throughout 4 months of maintenance and treatment and
6 months of non-treatment follow-up and the effect was not proven to be permanently effective
to smokers after the drug was discontinued. Smokers seemed to have quickly return to smoking
after the bupropion treatment (9).

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Methods to Test Suicidal/ Self-injurious Behavior
To test varencline and bupropion on the effects of suicidal behavior, a Standardized
MedDRA Query was used. For Suicide/ self-injury to select cases that included any of the 11
specialized medical terms. To identify depression cases scientists matched any of the 22 terms in
the narrow scope SMQ for Depression (excluding suicide and self-injury) (14). Standardized
MedDRA Query is a database that groups terms being used to test a specific interest in a study.
They are intended to aid in case identification. The including terms may relate to signs,
symptoms, diagnoses, syndromes, physical findings, laboratory, and other psychological test
data, etc., related to the medical condition or area of interest (SMQs). In this study, smoking
cessation in relation to depression and suicide/ self-injury cases are the area of interest.
Results
Although there were many studies conducted to test the effects of varencline, data seems
to be insufficient. Conducted in Gass’s experiment, of the 60 participants enrolled at the visit, 59
remained in the study through week 5. One participant dropped out between weeks 4 and 5.
Three participants were missing entire weeks of data (12).
With insufficient data and missing participants from Gass’s study, results are incomplete.
When varenicline and bupropion were conducted in the same experiment with Moore, T.J. the
main outcome measure we identified 3,249 reported events of suicidal/self-injurious behavior or
depression, 2,925 for varenicline, 229 for bupropion. Both drugs caused suicide attempt cases,
varencline was associated with 272 of295 of smoking treatment cases, bupropion for 19 cases
(14).

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Conclusion
Depressive disorders in relation to smoking cessation still remain a mystery. It is still
undetermined if bupropion and varencline should be used either alone or together to treat
smoking cessation, and more research is still needed. Testing smoking cessation without
treatments should be tested to determine if first of all depression is even a factor. Then, if
depression is not related, test the groups of smokers depending on stability, such as previous
history of depression or psychiatric disorders. Varenicline in the current research found should
not be distributed to anyone with psychiatric illness or history of depression, due to the
dangerous side effects or depression and suicidal behavior and thoughts. Bupropion is simply
just an anti-depressant used to suppress levels of depression during smoking cessation
treatments. A smoking cessation treatment along with an anti-depressant seem to be necessary
while a smoker undergoes smoking cessation, and a permanent effect needs to take place so that
after treatments, they continue smoke free.

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References
[1] Ascher, J. A., Cole, J. O., Colin, J. N., Feighner, J. P., Ferris, R. M., Fibiger, H. C., . . .
Richelson, E. (1995). Bupropion: A review of its mechanism of antidepressant activity. The
Journal of Clinical Psychiatry, 56(9), 395-401.
[2] Ashare, R. L., & McKee, S. A. (2012). Effects of varenicline and bupropion on cognitive
processes among nicotine-deprived smokers. Experimental and Clinical
Psychopharmacology, 20(1), 63-70. doi:10.1037/a0025594
[3] Berlin, I., Covey, L. S., Donohue, M. C., & Agostiv, V. (2011). Duration of smoking
abstinence and suicide-related outcomes. Nicotine & Tobacco Research, 13(10), 887-893.
doi:10.1093/ntr/ntr089
[4] Bupropion Information from Drugs.com. (n.d.). Drugs.com | Prescription Drug Information,
Interactions & Side Effects. Retrieved April 9, 2012, from
http://www.drugs.com/bupropion.html
[5] Bupropion - PubMed Health. (2009, October 1). National Center for Biotechnology
Information. Retrieved April 9, 2012, from
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000970/
[6] Busch, A. M., Wagener, T. L., Gregor, K. L., Ring, K. T., & Borrelli, B. (2011). Utilizing
reliable and clinically significant change criteria to assess for the development of depression
during smoking cessation treatment: The importance of tracking idiographic
change. Addictive Behaviors, 36(12), 1228-1232. doi:10.1016/j.addbeh.2011.07.031

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[7] Chee, C. (n.d.). 15 Nicotine Facts Everyone Ought To Know About. Interesting. Informative.
. Retrieved April 10, 2012, from http://odyb.net/mental-health/15-nicotine-facts-
everyone-ought-to-know-about/
[8] Chronic Disease Prevention and Health Promotion. (n.d.). CDC - Fact Sheet - Adult Cigarette
Smoking in the United States - Smoking & Tobacco Use. Centers for Disease Control and
Prevention. Retrieved April 2, 2012, from
http://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm#r
ef
[9] Covey, L. S., Glassman, A. H., Jiang, H., Fried, J., Masmela, J., LoDuca, C., . . . Rodriguez,
K. (2007). A randomized trial of bupropion and/or nicotine gum as maintenance treatment
for preventing smoking relapse.Addiction, 102(8), 1292-1302. doi:10.1111/j.1360-
0443.2007.01887.x
[10] Covey, L. S., Glassman, A. H., Jiang, H., Fried, J., Masmela, J., LoDuca, C., . . . Rodriguez,
K. (2007). A randomized trial of bupropion and/or nicotine gum as maintenance treatment
for preventing smoking relapse.Addiction, 102(8), 1292-1302. doi:10.1111/j.1360-
0443.2007.01887.x
[11] DiPaula, B. A., & Thomas, M. D. (2009). Worsening psychosis induced by varenicline in a
hospitalized psychiatric patient. Pharmacotherapy, 29(7), 852-857.
[12] Gass, J. C., Wray, J. M., Hawk, L. W., Mahoney, M. C., & Tiffany, S. T. (2012). Impact of
varenicline on cue-specific craving assessed in the natural environment among treatment-
seeking smokers.Psychopharmacology, doi:10.1007/s00213-012-2698-9

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[13] McClure, J. B., Swan, G. E., Catz, S. L., Jack, L., Javitz, H., McAfee, T., . . . Zbikowski, S.
M. (2010). Smoking outcome by psychiatric history after behavioral and varenicline
treatment. Journal of Substance Abuse Treatment, 38(4), 394-402.
doi:10.1016/j.jsat.2010.03.007
[14] Moore, T. J., Furberg, C. D., Glenmullen, J., Maltsberger, J. T., & Singh, S. (2011). Suicidal
behavior and depression in smoking cessation treatments. PloS One, 6(11), e27016.
doi:10.1371/journal.pone.0027016
[15] Nicotine | Psychology Today. (n.d.). Psychology Today: Health, Help, Happiness + Find a
Therapist. Retrieved April 10, 2012, from
http://www.psychologytoday.com/conditions/nicotine
[16] NIDA for Teens: Mind Over Matter - Tobacco Addiction - Page 2. (n.d.). NIDA for Teens:
The Science Behind Drug Abuse. Retrieved April 3, 2012, from
http://teens.drugabuse.gov/mom/mom_nic2.php
[17] Preda, A. (n.d.). Dopamine | Psychology Today. Psychology Today: Health, Help,
Happiness + Find a Therapist. Retrieved April 10, 2012, from
http://www.psychologytoday.com/basics/dopamine
[18] Standardised MedDRA Queries (SMQs) | MedDRA MSSO. (n.d.). MedDRA MSSO
Welcome. Retrieved April 3, 2012, from
http://www.meddramsso.com/subscriber_smq.asp
[19] Varenicline - PubMed Health. (n.d.). National Center for Biotechnology Information.
Retrieved April 2, 2012, from

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http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000351/
[20] Xi, Z. X. (2010). Preclinical pharmacology, efficacy and safety of varenicline in smoking
cessation and clinical utility in high risk patients. Drug, Healthcare and Patient
Safety, 2010(2), 39-48. doi:10.2147/DHPS.S6299
[21] Zawertailo, L., Busto, U., & Selby, P. (2011). Current major depression and its role in
tobacco dependence: State effects on craving, dopamine release, and smoking
cessation. European Neuropsychopharmacology,21, S201-S202.

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Annotated Bibliography
1. Duration of Smoking Abstinence and Suicide-Related Outcomes
Berlin, I., Covey, L. S., Donohue, M. C., & Agostiv, V. (2011). Duration of smoking
abstinence and suicide-related outcomes. Nicotine & Tobacco Research, 13(10), 887-893.
doi:10.1093/ntr/ntr089
Berlin represented in his research that depressed mood and substance use disorders predicted
suicidal thoughts and suicide attempts. This research assessed participants through question
targeting about their moods and behaviors during smoking cessation. This study used varencline
and bupropion for treatments. Questions that occurred were “suicide related outcomes were
associated with current smoking, successful smoking cessation, medications as an aid to smoking
cessation, or to an underlying mental disorder.”
This information is useful, because it has common information such as the treatments used which
is varenicline and bupropion. It also states some questions that remain which is essential
information for my research review.
2. Utilizing reliable and clinically significant change criteria to assess for the development
of depression during smoking cessation treatment: The importance of tracking idiographic
change
Busch, A. M., Wagener, T. L., Gregor, K. L., Ring, K. T., & Borrelli, B. (2011). Utilizing
reliable and clinically significant change criteria to assess for the development of depression
during smoking cessation treatment: The importance of tracking idiographic change. Addictive
Behaviors, 36(12), 1228-1232. doi:10.1016/j.addbeh.2011.07.031
Studies in this article state that smoking cessation either has no effect of significantly decreases
depressed mood, while others report that smoking cessation significantly increases depressed
mood. This results in an insufficient amount of data with mixed results. Questions remain about
increased depressive disorders during smoking cessation.
This article is useful, because it relates to the previous article about smoking cessation in
relationship to suicidal/depressive behavior. It also shows insufficient results which is useful for
answering the question what questions remain.
3. Differential Effects of Depression on Smoking Cessation in a Diverse Sample of Smokers
in Treatment
Castro, Y., Costello, T. J., Correa-Fernandez, V., Heppner, W. L., Reitzel, L. R., Cofta-Woerpel,
L., . . . Wetter, D. W. (2011). Differential effects of depression on smoking cessation in a diverse
sample of smokers in treatment. American Journal of Preventive Medicine, 41(1), 84-87.
doi:10.1016/j.amepre.2011.03.003
Summary: This study was conducted to demonstrate that different race and ethnicities have
different rates of depression due to smoking cessation. This study also narrows down how

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smoking cessation treatments may not be successful for specific races and ethnicities, such as
Latinos.
This study is useful, because it takes a more specific view in researching smoking cessation
among race and ethnicities. Other studies I have found use a more broad scale of people in their
studies, whether it be strictly women or no gender or race mentioned at all. The study may not be
useful ue to the limitations. One of which was a short term abstinence period for participants.
4. Smoking Cessation and the course of major depression: a follow up study
Glassman, A. H., Covey, L. S., Stetner, F., & Rivelli, S.357(9272), 1932. Retrieved
from http://linkinghub.elsevier.com/retrieve/pii/S0140673600050649
Smokers were asked to undergo abstinence from smoking and were checked up on after 6
months. At about 6 months, smokers were seen to have major depression effects. The study
included people who were willing to quit smoking, and those who quit in the middle of the
procedure were not accounted for. Smokers who recently had depression problems and had
undergone the study ended up having a reoccurrence of depression rates. Bupropion was used as
a treatment.
This information if useful because it provides me with evidence that smoking cessation is indeed
related to depression rates. Unfortunately, the study provided information that it was not accurate
to study people who abstained from smoking for 6 months, because you cannot continuously
keep watch on the group. Results from nine participants had chosen to continue smoking after
the experiment and developed clinical depression.
5. Suicidal Behavior and Depression in Smoking Cessation Treatments
Moore, T. J., Furberg, C. D., Glenmullen, J., Maltsberger, J. T., & Singh, S. (2011). Suicidal
behavior and depression in smoking cessation treatments. PloS One, 6(11), e27016.
doi:10.1371/journal.pone.0027016
Two treatments:
Varenicline (9575 tested)
Bupropion (1751 tested)
Nicotine replacement (1917)
Total: 3249 cases of suicidal/ self-injurious behavior
Varenicline-> 2925 cases (90%)
Bupropion -> 229 (7%)
Nicotine Replacement -> 95 (3%)
Varenicline shows a significant increase risk of reported depression and suicidal/self-injurious
behavior.
Summary: The purpose of this study was to compare three smoking cessation treatments to
determine which one had a higher suicidal/ self-injurious behavior and depression rate. They
compared varenicline and bupropion with nicotine replacement to see which one showed a
higher affect on suicide behavior.

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This source is useful because it gave a breakdown of which treatment was more harmful towards
smoking cessation. To test the levels of suicidal/ self-injury rates, they used Standardized
MedDRA Query. This method was used to measure harmful reactions towards suicidal/ self
injury behavior.